Genetic polymorphisms and benzene metabolism in humans exposed to a wide Range of air concentrations

Background Coagulation system is heavily involved into the process of infective endocarditis (IE) vegetation formation and can facilitate further embolization. In this study we aimed to assess the coagulation and platelet state in IE implementing a wide range of standard and global laboratory assays. We also aim to determine whether prothrombotic genetic polymorphisms play any role in embolization and mortality in IE patients. Methods 37 patients with IE were enrolled into the study. Coagulation was assessed using standard coagulation assays (activated partial thromboplastin time (APTT), prothrombin, fibrinogen, D-dimer concentrations) and integral assays (thromboelastography (TEG) and thrombodynamics (TD)). Platelet functional activity was estimated by flow cytometry. Single nuclear polymorphisms of coagulation system genes were studied. Results Fibrinogen concentration and fibrinogen-dependent parameters of TEG and TD were increased in patients indicating systemic inflammation. In majority of patients clot growth rate in thrombodynamics was significantly shifted towards hypercoagulation in consistency with D-dimers elevation. However, in some patients prothrombin, thromboelastography and thrombodynamics were shifted towards hypocoagulation. Resting platelets were characterized by glycoprotein IIb-IIIa activation and degranulation. In patients with fatal IE, we observed a significant decrease in fibrinogen and thrombodynamics. In patients with embolism, we observed a significant decrease in the TEG R parameter. No association of embolism or mortality with genetic polymorphisms was found in our cohort. Conclusions Our findings suggest that coagulation in patients with infective endocarditis is characterized by general hypercoagulability and platelet pre-activation. Some patients, however, have hypocoagulant coagulation profile, which presumably can indicate progressing of hypercoagulation into consumption coagulopathy.

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Personalized TMS: role of RNA genotyping

Mental Illness ◽

10.1108/mij-10-2019-0004 ◽

2019 ◽

Vol 11 (2) ◽

pp. 8-15

Author(s):

Shawna Chan ◽

Robert Bota

Keyword(s):

Treatment Response ◽

Genetic Polymorphisms ◽

Mental Illnesses ◽

Nucleotide Polymorphisms ◽

Noninvasive Brain Stimulation ◽

Single Nucleotide ◽

Content Type ◽

Wide Range ◽

Treatment Responses

Purpose Noninvasive brain stimulation (NIBS) such a transcranial magnetic stimulation, intermittent theta burst stimulation, transcranial direct current stimulation and electroconvulsive therapy have emerged as an efficacious and well-tolerated therapy for treatment-resistant psychiatric disorders. While novel NIBS techniques are an exciting addition to the current repertoire of neuropsychiatric therapies, their success is somewhat limited by the wide range of treatment responses seen among treated patients. Design/methodology/approach In this study, the authors will review the studies on relevant genetic polymorphisms and discuss the role of RNA genotyping in personalizing NIBS. Findings Genome studies have revealed several genetic polymorphisms that may contribute for the heterogeneity of treatment response to NIBS where the presence of certain single nucleotide polymorphisms (SNPs) are associated with responders versus nonresponders. Originality/value Historically, mental illnesses have been arguably some of the most challenging disorders to study and to treat because of the degree of biological variability across affected individuals, the role of genetic and epigenetic modifications, the diversity of clinical symptomatology and presentations and the interplay with environmental factors. In lieu of these challenges, there has been a push for personalized medicine in psychiatry that aims to optimize treatment response based on one’s unique characteristics.

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Cumulative frequency-dependent selective episodes allow for rapid morph cycles and rock-paper-scissors dynamics in species with overlapping generations

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2014.0976 ◽

2014 ◽

Vol 281 (1788) ◽

pp. 20140976 ◽

Cited By ~ 23

Author(s):

Luis M. San-Jose ◽

Miguel Peñalver-Alcázar ◽

Borja Milá ◽

Virginia Gonzalez-Jimena ◽

Patrick S. Fitze

Keyword(s):

Genetic Polymorphisms ◽

Overlapping Generations ◽

Offspring Survival ◽

Frequency Dependent ◽

Common Lizard ◽

Wide Range ◽

Zootoca Vivipara ◽

Almost All ◽

Morph Frequency ◽

Over Time

Rock-paper-scissors (RPS) dynamics, which maintain genetic polymorphisms over time through negative frequency-dependent (FD) selection, can evolve in short-lived species with no generational overlap, where they produce rapid morph frequency cycles. However, most species have overlapping generations and thus, rapid RPS dynamics are thought to require stronger FD selection, the existence of which yet needs to be proved. Here, we experimentally demonstrate that two cumulative selective episodes, FD sexual selection reinforced by FD selection on offspring survival, generate sufficiently strong selection to generate rapid morph frequency cycles in the European common lizard Zootoca vivipara , a multi-annual species with major generational overlap. These findings show that the conditions required for the evolution of RPS games are fulfilled by almost all species exhibiting genetic polymorphisms and suggest that RPS games may be responsible for the maintenance of genetic diversity in a wide range of species.

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The genetic basis of platelet responsiveness to clopidogrel

Thrombosis and Haemostasis ◽

10.1160/th11-04-0228 ◽

2011 ◽

Vol 106 (08) ◽

pp. 203-210 ◽

Cited By ~ 9

Author(s):

Paul Fefer ◽

Shlomi Matetzky

Keyword(s):

Coronary Artery Disease ◽

Genetic Polymorphisms ◽

Active Metabolite ◽

Genetic Basis ◽

Genetic Factors ◽

Platelet Inhibition ◽

Clinical Implications ◽

Wide Range ◽

Metabolite Generation ◽

Artery Disease

SummaryClopidogrel reduces ischaemic complications in a wide range of patients with coronary artery disease. However, there is much inter-individual variation in clopidogrel-induced platelet inhibition, and a substantial proportion of patients will exhibit non-responsiveness to clopidogrel. Multiple studies have demonstrated an association between the presence of genetic polymorphisms associated with suboptimal clopidogrel-active metabolite generation, decreased platelet responsiveness, and adverse clinical outcomes. However, it is not clear to what extent the genetic polymorphisms account for the observed variability in response to clopidogrel. In this review we provide a critical summary of the available evidence linking genetic factors with response to clopidogrel, and discuss the clinical implications of this association.

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Higher BMI, but not obesity-related genetic polymorphisms, correlates with lower structural connectivity of the reward network in a population-based study

International Journal of Obesity ◽

10.1038/s41366-020-00702-4 ◽

2020 ◽

Author(s):

Frauke Beyer ◽

Rui Zhang ◽

Markus Scholz ◽

Kerstin Wirkner ◽

Markus Loeffler ◽

...

Keyword(s):

Genetic Polymorphisms ◽

Genetic Variants ◽

Structural Connectivity ◽

Population Based ◽

Reward Processing ◽

Clustering Coefficient ◽

Graph Metrics ◽

Wide Range ◽

Reward Network ◽

Connectivity Strength

Abstract Background Obesity is of complex origin, involving genetic and neurobehavioral factors. Genetic polymorphisms may increase the risk for developing obesity by modulating dopamine-dependent behaviors, such as reward processing. Yet, few studies have investigated the association of obesity, related genetic variants, and structural connectivity of the dopaminergic reward network. Methods We analyzed 347 participants (age range: 20–59 years, BMI range: 17–38 kg/m2) of the LIFE-Adult Study. Genotyping for the single nucleotid polymorphisms rs1558902 (FTO) and rs1800497 (near dopamine D2 receptor) was performed on a microarray. Structural connectivity of the reward network was derived from diffusion-weighted magnetic resonance imaging at 3 T using deterministic tractography of Freesurfer-derived regions of interest. Using graph metrics, we extracted summary measures of clustering coefficient and connectivity strength between frontal and striatal brain regions. We used linear models to test the association of BMI, risk alleles of both variants, and reward network connectivity. Results Higher BMI was significantly associated with lower connectivity strength for number of streamlines (β = −0.0025, 95%—C.I.: [−0.004, −0.0008], p = 0.0042), and, to lesser degree, fractional anisotropy (β = −0.0009, 95%—C.I. [−0.0016, −0.00008], p = 0.031), but not clustering coefficient. Strongest associations were found for left putamen, right accumbens, and right lateral orbitofrontal cortex. As expected, the polymorphism rs1558902 in FTO was associated with higher BMI (F = 6.9, p < 0.001). None of the genetic variants was associated with reward network structural connectivity. Conclusions Here, we provide evidence that higher BMI correlates with lower reward network structural connectivity. This result is in line with previous findings of obesity-related decline in white matter microstructure. We did not observe an association of variants in FTO or near DRD2 receptor with reward network structural connectivity in this population-based cohort with a wide range of BMI and age. Future research should further investigate the link between genetics, obesity and fronto-striatal structural connectivity.

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Recent Applications of High Resolution Electron Microscopy to Crystalline Arrays of Virus Particles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100070199 ◽

1978 ◽

Vol 36 (3) ◽

pp. 470-482 ◽

Cited By ~ 1

Author(s):

R.W. Horne

Keyword(s):

Electron Microscopy ◽

Image Processing ◽

Analytical Techniques ◽

Staining Technique ◽

High Resolution Electron Microscopy ◽

Optical Diffraction ◽

Full Potential ◽

Virus Particles ◽

Resolution Electron ◽

Wide Range

The technique of surrounding virus particles with a neutralised electron dense stain was described at the Fourth International Congress on Electron Microscopy, Berlin 1958 (see Home & Brenner, 1960, p. 625). For many years the negative staining technique in one form or another, has been applied to a wide range of biological materials. However, the full potential of the method has only recently been explored following the development and applications of optical diffraction and computer image analytical techniques to electron micrographs (cf. De Hosier & Klug, 1968; Markham 1968; Crowther et al., 1970; Home & Markham, 1973; Klug & Berger, 1974; Crowther & Klug, 1975). These image processing procedures have allowed a more precise and quantitative approach to be made concerning the interpretation, measurement and reconstruction of repeating features in certain biological systems.

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Microfabrication research at the National Submicron Facility

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100074331 ◽

1983 ◽

Vol 41 ◽

pp. 86-89

Author(s):

E.D. Wolf

Keyword(s):

Integrated Circuits ◽

Particle Physics ◽

High Speed ◽

New Technology ◽

High Energy ◽

High Energy Particle ◽

New Science ◽

Wide Range ◽

Intermediate Domain ◽

Circuit Function

Most microelectronics devices and circuits operate faster, consume less power, execute more functions and cost less per circuit function when the feature-sizes internal to the devices and circuits are made smaller. This is part of the stimulus for the Very High-Speed Integrated Circuits (VHSIC) program. There is also a need for smaller, more sensitive sensors in a wide range of disciplines that includes electrochemistry, neurophysiology and ultra-high pressure solid state research. There is often fundamental new science (and sometimes new technology) to be revealed (and used) when a basic parameter such as size is extended to new dimensions, as is evident at the two extremes of smallness and largeness, high energy particle physics and cosmology, respectively. However, there is also a very important intermediate domain of size that spans from the diameter of a small cluster of atoms up to near one micrometer which may also have just as profound effects on society as “big” physics.

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Application of TEM to Deformation, Wear, and Fracture of Ceramics

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100052377 ◽

1974 ◽

Vol 32 ◽

pp. 472-473

Author(s):

B. J. Hockey

Keyword(s):

Wear Resistance ◽

High Temperature ◽

Mechanical Behavior ◽

Brittle Materials ◽

High Temperature Strength ◽

Wide Range ◽

Corrosive Environments ◽

Further Development

Ceramics, such as Al2O3 and SiC have numerous current and potential uses in applications where high temperature strength, hardness, and wear resistance are required often in corrosive environments. These materials are, however, highly anisotropic and brittle, so that their mechanical behavior is often unpredictable. The further development of these materials will require a better understanding of the basic mechanisms controlling deformation, wear, and fracture.The purpose of this talk is to describe applications of TEM to the study of the deformation, wear, and fracture of Al2O3. Similar studies are currently being conducted on SiC and the techniques involved should be applicable to a wide range of hard, brittle materials.

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Observation of Atom Rows in Thorium Pyromellitate Using a Field Emission STEM

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010007802x ◽

1977 ◽

Vol 35 ◽

pp. 80-81

Author(s):

H. Todokoro ◽

S. Nomura ◽

T. Komoda

Keyword(s):

Field Emission ◽

Amorphous Carbon ◽

Carbon Film ◽

Dark Field Image ◽

Dark Field ◽

Amorphous Carbon Film ◽

Atomic Size ◽

Wide Range ◽

A Chain

It is interesting to observe polymers at atomic size resolution. Some works have been reported for thorium pyromellitate by using a STEM (1), or a CTEM (2,3). The results showed that this polymer forms a chain in which thorium atoms are arranged. However, the distance between adjacent thorium atoms varies over a wide range (0.4-1.3nm) according to the different authors.The present authors have also observed thorium pyromellitate specimens by means of a field emission STEM, described in reference 4. The specimen was prepared by placing a drop of thorium pyromellitate in 10-3 CH3OH solution onto an amorphous carbon film about 2nm thick. The dark field image is shown in Fig. 1A. Thorium atoms are clearly observed as regular atom rows having a spacing of 0.85nm. This lattice gradually deteriorated by successive observations. The image changed to granular structures, as shown in Fig. 1B, which was taken after four scanning frames.

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Development of a conical anode Fe-gun for low voltage SEM

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100106958 ◽

1988 ◽

Vol 46 ◽

pp. 978-979

Author(s):

T. Miyokawa ◽

S. Norioka ◽

S. Goto

Keyword(s):

High Resolution ◽

Field Emission ◽

Low Voltage ◽

Irradiation Damage ◽

Cold Cathode ◽

Virtual Source ◽

Source Position ◽

Electrostatic Lens ◽

Electrostatic Lenses ◽

Wide Range

Field emission SEMs (FE-SEMs) are becoming popular due to their high resolution needs. In the field of semiconductor product, it is demanded to use the low accelerating voltage FE-SEM to avoid the electron irradiation damage and the electron charging up on samples. However the accelerating voltage of usual SEM with FE-gun is limited until 1 kV, which is not enough small for the present demands, because the virtual source goes far from the tip in lower accelerating voltages. This virtual source position depends on the shape of the electrostatic lens. So, we investigated several types of electrostatic lenses to be applicable to the lower accelerating voltage. In the result, it is found a field emission gun with a conical anode is effectively applied for a wide range of low accelerating voltages.A field emission gun usually consists of a field emission tip (cold cathode) and the Butler type electrostatic lens.

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